Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

Orthogonal Trajectories01:26

Orthogonal Trajectories

48
Orthogonal trajectories describe the geometric relationship between two families of curves that intersect each other at right angles. One illustrative case involves a family of parabolas that open sideways along the x-axis. These curves share a common shape but differ by a scaling parameter, resulting in a set of curves that all pass through the origin and widen at different rates.Determining Orthogonal TrajectoriesTo identify the orthogonal trajectories for these parabolas, the first step...
48
Switching of BJT01:22

Switching of BJT

853
Switching behavior in Bipolar Junction Transistors (BJTs) is a fundamental aspect utilized in various electronic circuits, particularly for digital logic applications like switches and amplifiers. In a typical switching circuit, a BJT alternates between cut-off and saturation modes, corresponding to the "off" and "on" states, respectively, thus behaving like an ideal switch.
Cut-off Mode ("Off" State): In this state, both the emitter-base and collector-base junctions are...
853
pH Regulation in Cells01:28

pH Regulation in Cells

7.6K
pH plays a critical role in maintaining normal cellular activities. It helps maintain the structure and function of various proteins, dictates the charge on cellular membranes, and is crucial for metabolic reactions inside the cell. Moreover, cells use the energy from the proton motive force to generate ATP.
Cytosolic pH
Under physiological conditions, the cytosolic pH is slightly more acidic than the extracellular pH. However, cells must prevent further acidification of their cytosol to...
7.6K
GTPases and their Regulation02:14

GTPases and their Regulation

9.8K
Guanine nucleotide-binding proteins (G-proteins), also known as GTPases, are a superfamily of proteins that regulate many cellular processes, such as cell signaling, vesicular transport, and the regulation of cell shape and motility. Mutation or dysfunction of these proteins can lead to disease. There are around 40,000 known G-proteins that can broadly be classified into two groups ‒  small G-proteins consisting of a single domain and large multi-domain G-proteins.
Large G-proteins,...
9.8K
Epigenetic Regulation01:46

Epigenetic Regulation

33.7K
Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
33.7K
Gene Therapy00:59

Gene Therapy

27.6K
Gene therapy is a technique where a gene is inserted into a person’s cells to prevent or treat a serious disease. The added gene may be a healthy version of the gene that is mutated in the patient, or it could be a different gene that inactivates or compensates for the patient’s disease-causing gene. For example, in patients with severe combined immunodeficiency (SCID) due to a mutation in the gene for the enzyme adenosine deaminase, a functioning version of the gene can be...
27.6K

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Clinical Spectrum of Hereditary Hemorrhagic Telangiectasia: Data from the Comprehensive HHT Outcomes Registry of the US (CHORUS).

Blood·2026
Same author

Artificial intelligence in telemedicine: Topic modelling and network analysis of patents (1992-2024).

Digital health·2026
Same author

Nintedanib-amplified effects of HSP47 siRNA on liver fibrosis therapy by inhibiting collagen secretion.

Journal of controlled release : official journal of the Controlled Release Society·2025
Same author

Cutaneous Mucormycosis in a Patient With Cirrhosis: A Case Report.

Journal of investigative medicine high impact case reports·2025
Same author

PSCA-targeted BPX-601 CAR T cells with pharmacological activation by rimiducid in metastatic pancreatic and prostate cancer: a phase 1 dose escalation trial.

Nature communications·2024
Same author

Natural endogenous material-based vehicles for delivery of macromolecular drugs.

Chinese journal of natural medicines·2024

Related Experiment Video

Updated: Jan 29, 2026

Generation of CAR T Cells for Adoptive Therapy in the Context of Glioblastoma Standard of Care
12:55

Generation of CAR T Cells for Adoptive Therapy in the Context of Glioblastoma Standard of Care

Published on: February 16, 2015

22.1K

Two-Dimensional Regulation of CAR-T Cell Therapy with Orthogonal Switches.

MyLinh T Duong1, Matthew R Collinson-Pautz1, Eva Morschl1

  • 1Bellicum Pharmaceuticals, 2130 W. Holcombe Blvd., Suite 800, Houston, TX 77030, USA.

Molecular Therapy Oncolytics
|February 12, 2019
PubMed
Summary
This summary is machine-generated.

This study introduces a dual-switch system for chimeric antigen receptor (CAR)-T cell therapy. The system enhances CAR-T cell expansion and persistence while offering a safety mechanism for controlled elimination, improving solid tumor treatment potential.

Keywords:
CAR-Tapoptosiscell therapycostimulation switchdimerizeriMCiRC9rapamycinrimiducidsafety switch

More Related Videos

A Spheroid Killing Assay by CAR T Cells
08:19

A Spheroid Killing Assay by CAR T Cells

Published on: December 12, 2018

17.2K
Studying Interactions between Myeloid Cells and CAR T Cells In Vitro and In Vivo
05:14

Studying Interactions between Myeloid Cells and CAR T Cells In Vitro and In Vivo

Published on: July 25, 2025

869

Related Experiment Videos

Last Updated: Jan 29, 2026

Generation of CAR T Cells for Adoptive Therapy in the Context of Glioblastoma Standard of Care
12:55

Generation of CAR T Cells for Adoptive Therapy in the Context of Glioblastoma Standard of Care

Published on: February 16, 2015

22.1K
A Spheroid Killing Assay by CAR T Cells
08:19

A Spheroid Killing Assay by CAR T Cells

Published on: December 12, 2018

17.2K
Studying Interactions between Myeloid Cells and CAR T Cells In Vitro and In Vivo
05:14

Studying Interactions between Myeloid Cells and CAR T Cells In Vitro and In Vivo

Published on: July 25, 2025

869

Area of Science:

  • Immunology
  • Oncology
  • Biotechnology

Background:

  • Chimeric antigen receptor (CAR)-T cell therapy shows efficacy in hematologic cancers but struggles with solid tumors due to limited T cell expansion and persistence.
  • Enhancing CAR-T cell activity is crucial for overcoming challenges in treating bulky and solid tumors.

Purpose of the Study:

  • To develop a novel, dual-switch system for enhancing CAR-T cell expansion and persistence.
  • To engineer a controllable safety mechanism for mitigating potential toxicities associated with enhanced CAR-T cells.

Main Methods:

  • Utilized rimiducid-inducible MyD88 and CD40 (iMC) signaling elements to create a potent activation switch.
  • Developed an orthogonally regulated, rapamycin-induced, caspase-9-based safety switch (iRC9) for inducible CAR-T cell elimination.
  • Evaluated the system's efficacy in vitro and in xenograft tumor models.

Main Results:

  • Rimiducid-induced iMC costimulation significantly enhanced CAR-T cell proliferation, cytokine secretion, and antitumor efficacy.
  • Rapamycin-mediated iRC9 dimerization induced rapid, dose-dependent apoptosis, demonstrating effective toxicity mitigation.
  • The dual-switch system promoted drug-dependent CAR-T cell expansion and prolonged persistence.

Conclusions:

  • The novel dual-switch system offers a promising strategy to improve CAR-T cell therapy for solid tumors.
  • This system enables controlled enhancement of CAR-T cell activity and provides a critical safety feature for managing toxicity.
  • The ability to regulate CAR-T cell expansion and persistence may overcome current limitations in adoptive cell therapy.